Kisspeptin inhibits cancer growth and metastasis via activation of EIF2AK2

Kim, Tae Hun; Cho, Sung‐Gook

doi:10.3892/mmr.2017.7578

Cited by 20 publications

(10 citation statements)

References 29 publications

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“…They were able to detect an inhibition of cell migration and invasion, as well as re-sensitization of cells to chemotherapeutics when KISS1 was re-expressed in PC3M cells that lack KISS1 (23). Similar results with inhibition of prostate cancer cell growth and metastasis have been demonstrated in a recent study by activation of eukaryotic translation initiation factor 2a kinase 2 (EIF2AK2) upon kisspeptin and KISS1R stimulation (64).…”

Section: Strong Kiss-r Immunohistochemical Expression (Ie) In Normasupporting

confidence: 70%

Expression of Kisspeptin (KISS1) and its Receptor GPR54 (KISS1R) in Prostate Cancer

et al. 2020

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Background/Aim: Prostate cancer (PCa) is the second most commonly diagnosed cancer in men. In contrast to localized disease, metastatic PCa leads to increased mortality. Κisspeptin (KISS1) functions as a metastasis suppressor in various cancers. The aim of this study was to detect the expression of KISS1 and its receptor GPR54 (KISS1R) in prostate cancer. Materials and Methods: The expression of KISS1 and KISS1R was examined in prostate cancer tissue specimens after radical prostatectomy. Results: A higher expression of KISS1 and KISS1R was shown in patients with localized tumors (Stage ≤IIb) compared to patients with advanced (Stage ≥III) tumor. High Gleason score PCa and higher prognostic groups patients showed a lower expression rate of both KISS1 and KISS1R. Conclusion: A down-regulation of KISS1-KISS1R system was detected in advanced prostate cancer. KISS1as tumor suppressor might be useful in the future for the diagnosis, risk assessment of prostate cancer progression, as well as a therapeutic target for aggressive tumors. Prostate cancer (PCa) is the second most commonly diagnosed cancer in men, with an estimated 1.1 million diagnoses worldwide in 2012, accounting for 15% of all cancers diagnosed (1). PSA screening has contributed to an early diagnosis of most prostate cancers (2). Therapeutic options for a localized prostate cancer include surgery and/or radiotherapy. Unfortunately, disease often progresses, as evidenced most often by rising prostate-specific antigen (PSA). Advanced prostate cancer or metastatic disease requires androgen deprivation therapy (3), which however is not curative. Progression to castration-resistant cancer stage often requires additional hormonal or chemotherapy-based interventions (4-7). Metastasis is the predominant cause of prostate cancer death (8), rather than the original tumor growth. Over the past two decades, a great variety of molecules have been investigated having a role in suppression of tumor metastasis (9) and have become the target of clinical and basic cancer research. The expression of kisspeptin (KISS1) and its receptor GPR54 (KISS1R) in prostate cancer has been examined within this study. The goal of our study was to find any existing correlation of KISS1 expression and/or KISS1R with different clinicopathological characteristics of prostate cancer. The findings might be useful in risk assessment of prostate cancer as well as in future development of cancer therapy and prevention of metastasis. Kisspeptin, KISS1, KISS1 gene, KISS1R, Kiss1r. Several terms that refer to kisspeptin and kisspeptin receptor have been used over the past years. In our study and in accordance to Human Genome Organization Gene Nomenclature Committee (HGNC), KISS1 is used to represent the human (primate) kisspeptin gene and Kiss1 to represent non-human (non-primate) kisspeptin genes. (10). Non-italicized versions of the gene nomenclature are used to refer to the protein products of KISS1 (KISS1 for human and Kiss1 for other species). The full-length peptide products of KISS1/Kiss1 ge...

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Section: Strong Kiss-r Immunohistochemical Expression (Ie) In Normasupporting

confidence: 70%

Expression of Kisspeptin (KISS1) and its Receptor GPR54 (KISS1R) in Prostate Cancer

et al. 2020

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“…To understand how kisspeptin might exert direct anti-metastatic effects in prostate cancer, KISS1 was re-expressed in PC3M cells that lack KISS1 and this resulted in an inhibition of cell migration and invasion and re-sensitization of cells to chemotherapeutics ( 10 ). Another study showed that KISS1R signaling induced the activation of eukaryotic translation initiation factor 2α kinase 2 (EIF2AK2) in prostate cancers and thereby inhibited cell growth and metastasis ( 69 ). Clearly, kisspeptin can act on prostate cancer cells both indirectly via the HPG axis and directly, thus its clinical value in treating prostate cancer is very promising and awaits further studies.…”

Section: Metastasis Suppressor Rolesmentioning

confidence: 99%

KISS1/KISS1R in Cancer: Friend or Foe?

Guzman

Brackstone

Radovick³

et al. 2018

Front. Endocrinol.

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The KISS1 gene encodes KISS1, a protein that is rapidly processed in serum into smaller but biologically active peptides called kisspeptins (KPs). KISS1 and the KPs signal via the G-protein coupled receptor KISS1R. While KISS1 and KPs are recognized as potent positive regulators of the reproductive neuroendocrine axis in mammals, the first reported role for KISS1 was that of metastasis suppression in melanoma. Since then, it has become apparent that KISS1, KPs, and KISS1R regulate the development and progression of several cancers but interestingly, while these molecules act as suppressors of tumorigenesis and metastasis in many cancers, in breast and liver cancer they function as promoters. Thus, they join a small but growing number of molecules that exhibit dual roles in cancer highlighting the importance of studying cancer in context. Given their roles, KISS1, KPs and KISS1R represent important molecules in the development of novel therapies and/or as prognostic markers in treating cancer. However, getting to that point requires a detailed understanding of the relationship between these molecules and different cancers. The purpose of this review is therefore to highlight and discuss the clinical studies that have begun describing this relationship in varying cancer types including breast, liver, pancreatic, colorectal, bladder, and ovarian. An emerging theme from the reviewed studies is that the relationship between these molecules and a given cancer is complex and affected by many factors such as the micro-environment and steroid receptor status of the cancer cell. Our review and discussion of these important clinical studies should serve as a valuable resource in the successful development of future clinical studies.

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“…For example, the upregulation of Sox2 in breast cancer tissues was associated with lymph node metastasis, pathological grade and TNM classification (6). Kisspeptin suppressed cancer growth and metastasis by activating EIF2AK2 in CRC (7). Cyclin D2/miR-1297 signaling was associated with the growth and metastasis of CRC (8).…”

Section: Introductionmentioning

confidence: 99%

BNIPL‑2 expression is correlated with the prognosis and regulates the proliferation of colorectal cancer through CD44

et al. 2019

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Colorectal cancer (CRC) currently leads to many deaths worldwide. The regulatory mechanism, however, remains largely unclear. In the present study, bioinformatics methods were used to identify genes associated with CRC prognosis and to detect the molecular signals regulating the cell cycle in two CRC cell lines. It was revealed that BNIPL-2 expression was higher in CRC tissues than in adjacent tissue samples. Upregulation of BNIPL-2 was correlated with poor prognosis and the adverse malignant stages T and M. BNIPL-2 was also associated with signaling pathways involved in cancer cell growth. BNIPL-2 overexpression promoted cell proliferation and increased the proportion of cells in the G2/M phase. Knockdown of BNIPL-2 inhibited cell proliferation. CD44 was regulated by BNIPL-2 and promoted cell proliferation. Downregulation of CD44 suppressed cell proliferation and rescued the cell proliferation promoted by BNIPL-2. Overexpression of CD44 restored the cell proliferation suppressed by BNIPL-2 knockdown. The present study not only suggested that BNIPL-2 may be a potential biomarker of CRC but also indicated that BNIPL-2 regulates CRC cancer proliferation via CD44, which could be a diagnostic and clinical treatment target.

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Kisspeptin inhibits cancer growth and metastasis via activation of EIF2AK2

Cited by 20 publications

References 29 publications

Expression of Kisspeptin (KISS1) and its Receptor GPR54 (KISS1R) in Prostate Cancer

Expression of Kisspeptin (KISS1) and its Receptor GPR54 (KISS1R) in Prostate Cancer

KISS1/KISS1R in Cancer: Friend or Foe?

BNIPL‑2 expression is correlated with the prognosis and regulates the proliferation of colorectal cancer through CD44

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